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5. Conclusions

We succeeded in improving hematopoietic differentiation and

identifying optimal external environmental conditions for the mainte­

nance culture of hPSCs. We found the interaction between extracellular

matrix laminin and ITGB1 expressed on the hPSC surface modulates the

downstream ILK-canonical Wnt/β-catenin-pJUN signaling cascade to

have a significant effect on hematopoiesis. These results show that the

extracellular scaffolds used during the maintenance phase determine the

differentiation fate of hPSCs and might explain the discrepancies in

experimental results between laboratories that use the same differenti­

ation methods but different extracellular scaffolds in the maintenance

culture. Moreover, these findings will be useful for developing individ­

ualized medicine by regulating the differentiation capacity of patientderived hPSCs by simply changing the scaffold without any gene edit­

ing. Furthermore, by changing the concentration of the LM511-E8

extracellular environment and also adding bFGF, TGF-β, and heparin

reagents to the conventional hPSC-sac method, we succeeded in accel­

erating the production of definitive hematopoiesis and its yield. In the

basic research field of hematology, this study provides an easy and

efficient method to obtain HPCs and more definitive hematopoiesis in

vitro. This study thus should contribute to the development of regener­

ative medicine using hematopoietic lineages.

Declaration of Competing Interest

A.Y., S.N., K.S., and K.E. have applied for patents related to this

manuscript. K.S. is a cofounder and a shareholder of MATRIXOME, Inc.

K.E. is a founder of Megakaryon and a member of its scientific advisory

board without salary; the interests of K.E. were reviewed and are

managed by Kyoto University in accordance with its conflict-of-interest

policies.

Acknowledgments

The authors thank Ms. Toshie Kusunoki for assisting with the ex­

periments, Dr. Yoshihiro Iwamoto for technical advice, and Dr. Peter

Karagiannis for critical reading of the manuscript.

This work was supported in part by the Highway Program for Real­

ization of Regenerative Medicine (JP18bm0504008, K.E.) and the Core

Center for iPS Cell Research (JP18bm0104001, N.S, S.N., K.E.) from the

Japan Agency for Medical Research and Development (AMED), and by

Grant-in-Aid for JSPS fellow (JP18J14237, A.Y.) and for scientific

research (18H04164, K.E.) from the Japan Society for the Promotion of

Science (JSPS).

Appendix A. Supplementary data

Supplementary data to this article can be found online at https://doi.

org/10.1016/j.scr.2021.102287.

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