15
1. Calvo W (1968) The innervation of the bone marrow in laboratory animals. Am J
16
Anat 123:315-28 doi:10.1002/aja.1001230206
17
2. Pinho S, Frenette PS (2019) Haematopoietic stem cell activity and interactions
18
with the niche. Nat Rev Mol Cell Biol 20:303-20 doi:10.1038/s41580-019-0103-9
19
3. Torres LS, Asada N, Weiss MJ, Trumpp A, Suda T, Scadden DT, Ito K (2022)
20
Recent advances in "sickle and niche" research - Tribute to Dr. Paul S Frenette.
21
Stem Cell Reports 17:1509-35 doi:10.1016/j.stemcr.2022.06.004
22
Asada N and Katayama Y
4. Nilsson SK, Johnston HM, Coverdale JA (2001) Spatial localization of
transplanted hemopoietic stem cells: inferences for the localization of stem cell
niches. Blood 97:2293-9 doi:10.1182/blood.v97.8.2293
5. Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP, Knight MC, Martin
RP, Schipani E, Divieti P, Bringhurst FR, Milner LA, Kronenberg HM, Scadden
DT (2003) Osteoblastic cells regulate the haematopoietic stem cell niche. Nature
425:841-6 doi:10.1038/nature02040
6. Zhang J, Niu C, Ye L, Huang H, He X, Tong WG, Ross J, Haug J, Johnson T,
Feng JQ, Harris S, Wiedemann LM, Mishina Y, Li L (2003) Identification of the
10
haematopoietic stem cell niche and control of the niche size. Nature 425:836-41
11
doi:10.1038/nature02041
12
7. Lymperi S, Horwood N, Marley S, Gordon MY, Cope AP, Dazzi F (2008) Strontium
13
can increase some osteoblasts without increasing hematopoietic stem cells.
14
Blood 111:1173-81 doi:10.1182/blood-2007-03-082800
15
8. Ma YD, Park C, Zhao H, Oduro KA, Jr., Tu X, Long F, Allen PM, Teitelbaum SL,
16
Choi K (2009) Defects in osteoblast function but no changes in long-term
17
repopulating potential of hematopoietic stem cells in a mouse chronic
18
inflammatory arthritis model. Blood 114:4402-10 doi:10.1182/blood-2008-12-
19
196311
20
9. Greenbaum A, Hsu YM, Day RB, Schuettpelz LG, Christopher MJ, Borgerding
21
JN, Nagasawa T, Link DC (2013) CXCL12 in early mesenchymal progenitors is
22
required for haematopoietic stem-cell maintenance. Nature 495:227-30
23
doi:10.1038/nature11926
24
10. Ding L, Saunders TL, Enikolopov G, Morrison SJ (2012) Endothelial and
23
Asada N and Katayama Y
perivascular cells maintain haematopoietic stem cells. Nature 481:457-62
doi:10.1038/nature10783
11. Cao H, Cao B, Heazlewood CK, Domingues M, Sun X, Debele E, McGregor NE,
Sims NA, Heazlewood SY, Nilsson SK (2019) Osteopontin is An Important
Regulative Component of the Fetal Bone Marrow Hematopoietic Stem Cell Niche.
Cells 8 doi:10.3390/cells8090985
12. Nilsson SK, Johnston HM, Whitty GA, Williams B, Webb RJ, Denhardt DT,
Bertoncello I, Bendall LJ, Simmons PJ, Haylock DN (2005) Osteopontin, a key
component of the hematopoietic stem cell niche and regulator of primitive
10
hematopoietic progenitor cells. Blood 106:1232-9 doi:10.1182/blood-2004-11-
11
4422
12
13. Ding L, Morrison SJ (2013) Haematopoietic stem cells and early lymphoid
13
progenitors
occupy
distinct
14
doi:10.1038/nature11885
bone
marrow
niches.
Nature
495:231-5
15
14. Yu VW, Saez B, Cook C, Lotinun S, Pardo-Saganta A, Wang YH, Lymperi S,
16
Ferraro F, Raaijmakers MH, Wu JY, Zhou L, Rajagopal J, Kronenberg HM, Baron
17
R, Scadden DT (2015) Specific bone cells produce DLL4 to generate thymus-
18
seeding
19
doi:10.1084/jem.20141843
progenitors
from
bone
marrow.
Exp
Med
212:759-74
20
15. Mizoguchi T, Pinho S, Ahmed J, Kunisaki Y, Hanoun M, Mendelson A, Ono N,
21
Kronenberg HM, Frenette PS (2014) Osterix marks distinct waves of primitive
22
and definitive stromal progenitors during bone marrow development. Dev Cell
23
29:340-9 doi:10.1016/j.devcel.2014.03.013
24
16. Yu VW, Lymperi S, Oki T, Jones A, Swiatek P, Vasic R, Ferraro F, Scadden DT
24
Asada N and Katayama Y
(2016) Distinctive Mesenchymal-Parenchymal Cell Pairings Govern B Cell
Differentiation
doi:10.1016/j.stemcr.2016.06.009
in
the
Bone
Marrow.
Stem
Cell
Reports
7:220-35
17. Rankin EB, Wu C, Khatri R, Wilson TL, Andersen R, Araldi E, Rankin AL, Yuan
J, Kuo CJ, Schipani E, Giaccia AJ (2012) The HIF signaling pathway in
osteoblasts directly modulates erythropoiesis through the production of EPO.
Cell 149:63-74 doi:10.1016/j.cell.2012.01.051
18. Bonewald LF, Johnson ML (2008) Osteocytes, mechanosensing and Wnt
signaling. Bone 42:606-15 doi:10.1016/j.bone.2007.12.224
10
19. Sato M, Asada N, Kawano Y, Wakahashi K, Minagawa K, Kawano H, Sada A,
11
Ikeda K, Matsui T, Katayama Y (2013) Osteocytes regulate primary lymphoid
12
organs
13
doi:10.1016/j.cmet.2013.09.014
and
fat
metabolism.
Cell
Metab
18:749-58
14
20. Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a
15
hierarchy that originates from a primitive hematopoietic cell. Nat Med 3:730-7
16
doi:10.1038/nm0797-730
17
21. Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden
18
M, Paterson B, Caligiuri MA, Dick JE (1994) A cell initiating human acute myeloid
19
leukaemia
20
doi:10.1038/367645a0
after
transplantation
into
SCID
mice.
Nature
367:645-8
21
22. Ishikawa F, Yoshida S, Saito Y, Hijikata A, Kitamura H et al. (2007)
22
Chemotherapy-resistant human AML stem cells home to and engraft within the
23
bone-marrow endosteal region. Nat Biotechnol 25:1315-21 doi:10.1038/nbt1350
24
23. Kode A, Manavalan JS, Mosialou I, Bhagat G, Rathinam CV, Luo N, Khiabanian
25
Asada N and Katayama Y
H, Lee A, Murty VV, Friedman R, Brum A, Park D, Galili N, Mukherjee S, Teruya-
Feldstein
Leukaemogenesis induced by an activating beta-catenin mutation in osteoblasts.
Nature 506:240-4 doi:10.1038/nature12883
J,
Raza A,
Rabadan
R,
Berman
E,
Kousteni
(2014)
24. Bowers M, Zhang B, Ho Y, Agarwal P, Chen CC, Bhatia R (2015) Osteoblast
ablation reduces normal long-term hematopoietic stem cell self-renewal but
accelerates leukemia development. Blood 125:2678-88 doi:10.1182/blood-2014-
06-582924
25. Mach DB, Rogers SD, Sabino MC, Luger NM, Schwei MJ, Pomonis JD, Keyser
10
CP, Clohisy DR, Adams DJ, O'Leary P, Mantyh PW (2002) Origins of skeletal
11
pain: sensory and sympathetic innervation of the mouse femur. Neuroscience
12
113:155-66 doi:10.1016/s0306-4522(02)00165-3
13
26. Abeynayake N, Arthur A, Gronthos S (2021) Crosstalk between skeletal and
14
neural
tissues
is
critical
15
doi:10.1016/j.bone.2020.115645
for
skeletal
health.
Bone
142:115645
16
27. Fujita S, Morikawa T, Tamaki S, Sezaki M, Takizawa H, Okamoto S, Kataoka K,
17
Takubo K (2022) Quantitative Analysis of Sympathetic and Nociceptive
18
Innervation Across Bone Marrow Regions in Mice. Exp Hematol 112-113:44-59
19
e6 doi:10.1016/j.exphem.2022.07.297
20
28. Lorenz MR, Brazill JM, Beeve AT, Shen I, Scheller EL (2021) A Neuroskeletal
21
Atlas: Spatial Mapping and Contextualization of Axon Subtypes Innervating the
22
Long Bones of C3H and B6 Mice. J Bone Miner Res 36:1012-25
23
doi:10.1002/jbmr.4273
24
29. Castaneda-Corral G, Jimenez-Andrade JM, Bloom AP, Taylor RN, Mantyh WG,
26
Asada N and Katayama Y
Kaczmarska MJ, Ghilardi JR, Mantyh PW (2011) The majority of myelinated and
unmyelinated sensory nerve fibers that innervate bone express the tropomyosin
receptor
doi:10.1016/j.neuroscience.2011.01.039
kinase
A.
Neuroscience
178:196-207
30. Grills BL, Schuijers JA, Ward AR (1997) Topical application of nerve growth factor
improves
fracture
healing
doi:10.1002/jor.1100150212
in
rats.
Orthop
Res
15:235-42
31. Wang L, Zhou S, Liu B, Lei D, Zhao Y, Lu C, Tan A (2006) Locally applied nerve
growth factor enhances bone consolidation in a rabbit model of mandibular
10
distraction osteogenesis. J Orthop Res 24:2238-45 doi:10.1002/jor.20269
11
32. Schinke T, Liese S, Priemel M, Haberland M, Schilling AF, Catala-Lehnen P,
12
Blicharski D, Rueger JM, Gagel RF, Emeson RB, Amling M (2004) Decreased
13
bone formation and osteopenia in mice lacking alpha-calcitonin gene-related
14
peptide. J Bone Miner Res 19:2049-56 doi:10.1359/JBMR.040915
15
33. Mrak E, Guidobono F, Moro G, Fraschini G, Rubinacci A, Villa I (2010) Calcitonin
16
gene-related peptide (CGRP) inhibits apoptosis in human osteoblasts by beta-
17
catenin stabilization. J Cell Physiol 225:701-8 doi:10.1002/jcp.22266
18
34. Wang L, Shi X, Zhao R, Halloran BP, Clark DJ, Jacobs CR, Kingery WS (2010)
19
Calcitonin-gene-related peptide stimulates stromal cell osteogenic differentiation
20
and inhibits RANKL induced NF-kappaB activation, osteoclastogenesis and bone
21
resorption. Bone 46:1369-79 doi:10.1016/j.bone.2009.11.029
22
35. Mori T, Ogata T, Okumura H, Shibata T, Nakamura Y, Kataoka K (1999)
23
Substance P regulates the function of rabbit cultured osteoclast; increase of
24
intracellular free calcium concentration and enhancement of bone resorption.
27
Asada N and Katayama Y
Biochem Biophys Res Commun 262:418-22 doi:10.1006/bbrc.1999.1220
36. Wang L, Zhao R, Shi X, Wei T, Halloran BP, Clark DJ, Jacobs CR, Kingery WS
(2009) Substance P stimulates bone marrow stromal cell osteogenic activity,
osteoclast differentiation, and resorption activity in vitro. Bone 45:309-20
doi:10.1016/j.bone.2009.04.203
37. Niedermair T, Schirner S, Seebroker R, Straub RH, Grassel S (2018) Substance
P modulates bone remodeling properties of murine osteoblasts and osteoclasts.
Sci Rep 8:9199 doi:10.1038/s41598-018-27432-y
38. Luo Y, Raible D, Raper JA (1993) Collapsin: a protein in brain that induces the
10
collapse
and
paralysis
of
neuronal
11
doi:10.1016/0092-8674(93)80064-l
growth
cones.
Cell
75:217-27
12
39. Behar O, Golden JA, Mashimo H, Schoen FJ, Fishman MC (1996) Semaphorin
13
III is needed for normal patterning and growth of nerves, bones and heart. Nature
14
383:525-8 doi:10.1038/383525a0
15
40. Hayashi M, Nakashima T, Taniguchi M, Kodama T, Kumanogoh A, Takayanagi H
16
(2012)
Osteoprotection
17
doi:10.1038/nature11000
by
semaphorin
3A.
Nature
485:69-74
18
41. Hayashi M, Nakashima T, Yoshimura N, Okamoto K, Tanaka S, Takayanagi H
19
(2019) Autoregulation of Osteocyte Sema3A Orchestrates Estrogen Action and
20
Counteracts
21
doi:10.1016/j.cmet.2018.12.021
22
Bone
Aging.
Cell
Metab
29:627-37
e5
42. Fukuda T, Takeda S, Xu R, Ochi H, Sunamura S et al. (2013) Sema3A regulates
23
bone-mass
accrual
through
24
doi:10.1038/nature12115
sensory
28
innervations.
Nature
497:490-3
Asada N and Katayama Y
43. Bajayo A, Bar A, Denes A, Bachar M, Kram V, Attar-Namdar M, Zallone A, Kovacs
KJ, Yirmiya R, Bab I (2012) Skeletal parasympathetic innervation communicates
central IL-1 signals regulating bone mass accrual. Proc Natl Acad Sci U S A
109:15455-60 doi:10.1073/pnas.1206061109
44. Chartier SR, Mitchell SAT, Majuta LA, Mantyh PW (2018) The Changing Sensory
and Sympathetic Innervation of the Young, Adult and Aging Mouse Femur.
Neuroscience 387:178-90 doi:10.1016/j.neuroscience.2018.01.047
45. Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker KL, Armstrong D,
Ducy P, Karsenty G (2002) Leptin regulates bone formation via the sympathetic
10
nervous system. Cell 111:305-17 doi:10.1016/s0092-8674(02)01049-8
11
46. Elefteriou F, Ahn JD, Takeda S, Starbuck M, Yang X, Liu X, Kondo H, Richards
12
WG, Bannon TW, Noda M, Clement K, Vaisse C, Karsenty G (2005) Leptin
13
regulation of bone resorption by the sympathetic nervous system and CART.
14
Nature 434:514-20 doi:10.1038/nature03398
15
47. Kajimura D, Hinoi E, Ferron M, Kode A, Riley KJ, Zhou B, Guo XE, Karsenty G
16
(2011) Genetic determination of the cellular basis of the sympathetic regulation
17
of bone mass accrual. J Exp Med 208:841-51 doi:10.1084/jem.20102608
18
48. Sato T, Abe T, Chida D, Nakamoto N, Hori N, Kokabu S, Sakata Y, Tomaru Y,
19
Iwata T, Usui M, Aiko K, Yoda T (2010) Functional role of acetylcholine and the
20
expression of cholinergic receptors and components in osteoblasts. FEBS Lett
21
584:817-24 doi:10.1016/j.febslet.2010.01.001
22
49. Sato T, Abe T, Nakamoto N, Tomaru Y, Koshikiya N, Nojima J, Kokabu S, Sakata
23
Y, Kobayashi A, Yoda T (2008) Nicotine induces cell proliferation in association
24
with cyclin D1 up-regulation and inhibits cell differentiation in association with
29
Asada N and Katayama Y
p53 regulation in a murine pre-osteoblastic cell line. Biochem Biophys Res
Commun 377:126-30 doi:10.1016/j.bbrc.2008.09.114
50. Mandl P, Hayer S, Karonitsch T, Scholze P, Gyori D, Sykoutri D, Bluml S, Mocsai
A, Poor G, Huck S, Smolen JS, Redlich K (2016) Nicotinic acetylcholine
receptors
doi:10.1186/s13075-016-0961-x
modulate
osteoclastogenesis.
Arthritis
Res
Ther
18:63
51. Mito K, Sato Y, Kobayashi T, Miyamoto K, Nitta E, Iwama A, Matsumoto M,
Nakamura M, Sato K, Miyamoto T (2017) The nicotinic acetylcholine receptor
alpha7 subunit is an essential negative regulator of bone mass. Sci Rep 7:45597
10
doi:10.1038/srep45597
11
52. Somm E, Guerardel A, Maouche K, Toulotte A, Veyrat-Durebex C, Rohner-
12
Jeanrenaud F, Maskos U, Huppi PS, Schwitzgebel VM (2014) Concomitant
13
alpha7 and beta2 nicotinic AChR subunit deficiency leads to impaired energy
14
homeostasis and increased physical activity in mice. Mol Genet Metab 112:64-
15
72 doi:10.1016/j.ymgme.2014.03.003
16
53. Shi Y, Oury F, Yadav VK, Wess J, Liu XS, Guo XE, Murshed M, Karsenty G (2010)
17
Signaling through the M(3) muscarinic receptor favors bone mass accrual by
18
decreasing
19
doi:10.1016/j.cmet.2010.01.005
sympathetic
activity.
Cell
Metab
11:231-8
20
54. Pareyson D, Marchesi C (2009) Diagnosis, natural history, and management of
21
Charcot-Marie-Tooth disease. Lancet Neurol 8:654-67 doi:10.1016/S1474-
22
4422(09)70110-3
23
55. Pouwels S, de Boer A, Leufkens HG, Weber WE, Cooper C, de Vries F (2014)
24
Risk of fracture in patients with Charcot-Marie-Tooth disease. Muscle Nerve
30
Asada N and Katayama Y
50:919-24 doi:10.1002/mus.24240
56. Abdala R, Levi L, Longobardi V, Zanchetta MB (2020) Severe bone
microarchitecture deterioration in a family with hereditary neuropathy: evidence
of
doi:10.1007/s00198-020-05674-9
the
key
role
of
the
mechanostat.
Osteoporos
Int
31:2477-80
57. Schwartzlow C, Kazamel M (2019) Hereditary Sensory and Autonomic
Neuropathies: Adding More to the Classification. Curr Neurol Neurosci Rep 19:52
doi:10.1007/s11910-019-0974-3
58. Maayan C, Bar-On E, Foldes AJ, Gesundheit B, Pollak RD (2002) Bone mineral
10
density and metabolism in familial dysautonomia. Osteoporos Int 13:429-33
11
doi:10.1007/s001980200050
12
59. Maayan C, Becker Y, Gesundheit B, Girgis SI (2001) Calcitonin gene related
13
peptide
in
familial
dysautonomia.
14
doi:10.1054/npep.2001.0863
Neuropeptides
35:189-95
15
60. Katayama Y, Battista M, Kao WM, Hidalgo A, Peired AJ, Thomas SA, Frenette
16
PS (2006) Signals from the sympathetic nervous system regulate hematopoietic
17
stem
18
doi:10.1016/j.cell.2005.10.041
cell
egress
from
bone
marrow.
Cell
124:407-21
19
61. Kawamori Y, Katayama Y, Asada N, Minagawa K, Sato M, Okamura A,
20
Shimoyama M, Nakagawa K, Okano T, Tanimoto M, Kato S, Matsui T (2010) Role
21
for vitamin D receptor in the neuronal control of the hematopoietic stem cell niche.
22
Blood 116:5528-35 doi:10.1182/blood-2010-04-279216
23
62. Asada N, Katayama Y, Sato M, Minagawa K, Wakahashi K, Kawano H, Kawano
24
Y, Sada A, Ikeda K, Matsui T, Tanimoto M (2013) Matrix-embedded osteocytes
31
Asada N and Katayama Y
regulate mobilization of hematopoietic stem/progenitor cells. Cell Stem Cell
12:737-47 doi:10.1016/j.stem.2013.05.001
63. Lucas D, Bruns I, Battista M, Mendez-Ferrer S, Magnon C, Kunisaki Y, Frenette
PS (2012) Norepinephrine reuptake inhibition promotes mobilization in mice:
potential
doi:10.1182/blood-2011-07-367102
impact
to
rescue
low
stem
cell
yields.
Blood
119:3962-5
64. Kawano Y, Fukui C, Shinohara M, Wakahashi K, Ishii S, Suzuki T, Sato M, Asada
N, Kawano H, Minagawa K, Sada A, Furuyashiki T, Uematsu S, Akira S, Uede T,
Narumiya S, Matsui T, Katayama Y (2017) G-CSF-induced sympathetic tone
10
provokes fever and primes antimobilizing functions of neutrophils via PGE2.
11
Blood 129:587-97 doi:10.1182/blood-2016-07-725754
12
65. Yamazaki S, Ema H, Karlsson G, Yamaguchi T, Miyoshi H, Shioda S, Taketo MM,
13
Karlsson S, Iwama A, Nakauchi H (2011) Nonmyelinating Schwann cells
14
maintain hematopoietic stem cell hibernation in the bone marrow niche. Cell
15
147:1146-58 doi:10.1016/j.cell.2011.09.053
16
66. Liu Y, Chen Q, Jeong HW, Han D, Fabian J, Drexler HCA, Stehling M, Scholer
17
HR, Adams RH (2021) Dopamine signaling regulates hematopoietic stem and
18
progenitor cell function. Blood 138:2051-65 doi:10.1182/blood.2020010419
19
67. Mendez-Ferrer S, Lucas D, Battista M, Frenette PS (2008) Haematopoietic stem
20
cell release is regulated by circadian oscillations. Nature 452:442-7
21
doi:10.1038/nature06685
22
68. Mendez-Ferrer S, Michurina TV, Ferraro F, Mazloom AR, Macarthur BD, Lira SA,
23
Scadden DT, Ma'ayan A, Enikolopov GN, Frenette PS (2010) Mesenchymal and
24
haematopoietic stem cells form a unique bone marrow niche. Nature 466:829-34
32
Asada N and Katayama Y
doi:10.1038/nature09262
69. Lucas D, Scheiermann C, Chow A, Kunisaki Y, Bruns I, Barrick C, Tessarollo L,
Frenette PS (2013) Chemotherapy-induced bone marrow nerve injury impairs
hematopoietic regeneration. Nat Med 19:695-703 doi:10.1038/nm.3155
70. Geiger H, de Haan G, Florian MC (2013) The ageing haematopoietic stem cell
compartment. Nat Rev Immunol 13:376-89 doi:10.1038/nri3433
71. Maryanovich M, Zahalka AH, Pierce H, Pinho S, Nakahara F, Asada N, Wei Q,
Wang X, Ciero P, Xu J, Leftin A, Frenette PS (2018) Adrenergic nerve
degeneration in bone marrow drives aging of the hematopoietic stem cell niche.
10
Nat Med 24:782-91 doi:10.1038/s41591-018-0030-x
11
72. Ho YH, Del Toro R, Rivera-Torres J, Rak J, Korn C et al. (2019) Remodeling of
12
Bone Marrow Hematopoietic Stem Cell Niches Promotes Myeloid Cell Expansion
13
during Premature or Physiological Aging. Cell Stem Cell 25:407-18 e6
14
doi:10.1016/j.stem.2019.06.007
15
73. Li H, Qu J, Zhu H, Wang J, He H, Xie X, Wu R, Lu Q (2021) CGRP Regulates
16
the Age-Related Switch Between Osteoblast and Adipocyte Differentiation. Front
17
Cell Dev Biol 9:675503 doi:10.3389/fcell.2021.675503
18
74. Pierce H, Zhang D, Magnon C, Lucas D, Christin JR, Huggins M, Schwartz GJ,
19
Frenette PS (2017) Cholinergic Signals from the CNS Regulate G-CSF-Mediated
20
HSC Mobilization from Bone Marrow via a Glucocorticoid Signaling Relay. Cell
21
Stem Cell 20:648-58 e4 doi:10.1016/j.stem.2017.01.002
22
75. Garcia-Garcia A, Korn C, Garcia-Fernandez M, Domingues O, Villadiego J,
23
Martin-Perez D, Isern J, Bejarano-Garcia JA, Zimmer J, Perez-Simon JA, Toledo-
24
Aral JJ, Michel T, Airaksinen MS, Mendez-Ferrer S (2019) Dual cholinergic
33
Asada N and Katayama Y
signals regulate daily migration of hematopoietic stem cells and leukocytes.
Blood 133:224-36 doi:10.1182/blood-2018-08-867648
76. Fielding C, Garcia-Garcia A, Korn C, Gadomski S, Fang Z, Reguera JL, Perez-
Simon JA, Gottgens B, Mendez-Ferrer S (2022) Cholinergic signals preserve
haematopoietic stem cell quiescence during regenerative haematopoiesis. Nat
Commun 13:543 doi:10.1038/s41467-022-28175-1
77. Hill EL, Elde R (1991) Distribution of CGRP-, VIP-, D beta H-, SP-, and NPY-
immunoreactive nerves in the periosteum of the rat. Cell Tissue Res 264:469-80
doi:10.1007/BF00319037
10
78. Gao X, Zhang D, Xu C, Li H, Caron KM, Frenette PS (2021) Nociceptive nerves
11
regulate
haematopoietic
stem
12
doi:10.1038/s41586-020-03057-y
cell
mobilization.
Nature
589:591-96
13
79. Zahalka AH, Arnal-Estape A, Maryanovich M, Nakahara F, Cruz CD, Finley LWS,
14
Frenette PS (2017) Adrenergic nerves activate an angio-metabolic switch in
15
prostate cancer. Science 358:321-26 doi:10.1126/science.aah5072
16
80. Hanoun M, Zhang D, Mizoguchi T, Pinho S, Pierce H, Kunisaki Y, Lacombe J,
17
Armstrong SA, Duhrsen U, Frenette PS (2014) Acute myelogenous leukemia-
18
induced
19
hematopoietic
20
doi:10.1016/j.stem.2014.06.020
sympathetic
stem
neuropathy
cell
promotes
niche.
Cell
malignancy
Stem
in
Cell
an
altered
15:365-75
21
81. Arranz L, Sanchez-Aguilera A, Martin-Perez D, Isern J, Langa X, Tzankov A,
22
Lundberg P, Muntion S, Tzeng YS, Lai DM, Schwaller J, Skoda RC, Mendez-
23
Ferrer S (2014) Neuropathy of haematopoietic stem cell niche is essential for
24
myeloproliferative neoplasms. Nature 512:78-81 doi:10.1038/nature13383
34
Asada N and Katayama Y
82. Baryawno N, Przybylski D, Kowalczyk MS, Kfoury Y, Severe N, Gustafsson K,
Kokkaliaris KD, Mercier F, Tabaka M, Hofree M, Dionne D, Papazian A, Lee D,
Ashenberg O, Subramanian A, Vaishnav ED, Rozenblatt-Rosen O, Regev A,
Scadden DT (2019) A Cellular Taxonomy of the Bone Marrow Stroma in
Homeostasis
doi:10.1016/j.cell.2019.04.040
and
Leukemia.
Cell
177:1915-32
e16
83. Tikhonova AN, Dolgalev I, Hu H, Sivaraj KK, Hoxha E et al. (2019) The bone
marrow
microenvironment
at
doi:10.1038/s41586-019-1104-8
single-cell
resolution.
Nature
569:222-28
10
84. Baccin C, Al-Sabah J, Velten L, Helbling PM, Grunschlager F, Hernandez-
11
Malmierca P, Nombela-Arrieta C, Steinmetz LM, Trumpp A, Haas S (2020)
12
Combined single-cell and spatial transcriptomics reveal the molecular, cellular
13
and spatial bone marrow niche organization. Nat Cell Biol 22:38-48
14
doi:10.1038/s41556-019-0439-6
15
16
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Figure legends
18
Figure 1. The roles of bone cells and PNS in hematologic malignancies.
19
Constitutive activation of β-catenin in mature osteoblasts enhances the production
20
of the Notch ligand jagged 1(Jag1) in osteoblasts, which leads to the activation of
21
Notch signaling in HSC and promotes the leukemic transformation. Leukemic cells
22
release IL-1β, an inflammatory cytokine, causing the sympathetic neuropathy in the
23
bone marrow, resulting in the decrease of NE signals. Attenuated NE signaling via
35
Asada N and Katayama Y
β2-AR on nestin-positive niche cells downregulates the expression levels of niche
factors essential for HSC maintenance, which turn in results in the normal HSC
distinction in the leukemic bone marrow. LSC, leukemic stem cell.
Figure 2. Roles of the sensory nerve in bone remodeling. CGRP from sensory
nerve induce osteoblast differentiation via CALCRL/RAMP1 receptor complex and
suppresses the differentiation of osteoclast, resulting in the facilitation of bone
formation. Substance P (SP) promotes macrophage differentiation into osteoclasts,
which promotes osteoclast bone resorption function, but also promotes osteoblast
10
function, which in turn contributes to bone formation. NK1R, neurokinin 1 receptor.
11
12
Figure 3. Hematopoietic regulation by PNS in the bone marrow. G-CSF
13
treatment elicits the NE surge in the bone marrow by suppressing NE reuptake at
14
sympathetic nerve endings, which in turn the suppression of both osteoblasts and
15
osteocytes via β2-AR. NE-β2-AR signaling also stimulates the production of PGE2
16
from neutrophils during the G-CSF-induced HSC mobilization, leading to a febrile
17
side effect. Dopamine also contributes to the HSC maintenance via D2-type receptor
18
(D2R) signaling. Nonmyelinating Schwann cells, wrapping the sympathetic nerves,
19
function as niche cells by transforming TGF-β from latent form into activated form.
20
CGRP released from sensory nerves binds to CALCRL/RAMP1 receptor complex
21
on HSCs and promotes HSC chemotaxis by activating downstream signaling.
36
Asada N and Katayama Y
Capsaicin containing diet, which stimulates nociceptive nerve activity, increases the
efficiency of HSC mobilization.
37
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