US 201403297.04A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0329704 A1 Melton et al. (43) Pub. Date: Nov. 6, 2014 (54) MARKERS FORMATURE BETA-CIELLS AND Publication Classification METHODS OF USING THE SAME (51) Int. C. (71) Applicant: President and Fellows of Harvard College, Cambridge, MA (US) CI2O I/68 (2006.01) (52) U.S. C. (72) Inventors: Douglas A. Melton, Lexington, MA CPC ........ CI2O I/6881 (2013.01); C12O 2600/158 (US); Sinisa Hrvatin, Cambridge, MA (2013.01); C12O 2600/136 (2013.01) (US) USPC ............................... 506/9: 435/375; 435/6. 12 (21) Appl. No.: 14/228,959 (22) Filed: Mar 28, 2014 (57) ABSTRACT Related U.S. Application Data (60) Provisional application No. 61/806,371, filed on Mar. Markers for mature B-cells and methods of using these mark 28, 2013. ers are disclosed. 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In some aspects, the present invention provides a RELATED APPLICATIONS method of identifying the functional maturity of B-cells, the 0001. This application claims the benefit of U.S. Provi method comprising: (a) obtaining a putative B-cellor a popu sional Application No. 61/806,371, filed Mar. 28, 2013. The lation of putative B-cells; and (b) detecting an expression entire teachings of the above application are incorporated level in the putative f3-cellor the population of putative B-cells herein by reference. of one or more genes listed in Table 2, Table 3 or Table 4, wherein: (i) an elevated level of expression of one or more GOVERNMENT SUPPORT genes listed in Table 1 or Table 2 in the putative B-cell or the population of putative B-cells indicates that the putative B-cell 0002 This invention was made with government support or the population of putative B-cells are functionally mature under 2 U01 DK072473-07 awarded by the National Insti B-cells; and (ii) an elevated level of expression of one or more tutes of Health. The government has certain rights in the genes listed in Table 3 or Table 4 in the putative B-cell or the invention. population of putative B-cells indicates that the putative B-cell or the population of putative B-cells are functionally imma BACKGROUND OF THE INVENTION ture f3-cells. 0003. The directed differentiation of stem cells has the 0008. In some aspects, the present invention provides a potential to produce B-cells for administration to individuals method of identifying mature B-cells, the method compris Suffering from diseases associated with n-cell abnormality ing: (a) obtaining a putative B-cell or a population of putative (e.g., diabetes). However, existing in vitro differentiation pro B-cells; and (b) detecting an expression level in the putative tocols often produce “B-like cells, which do not have the B-cell or the population of putative B-cells of one or more same functional properties as mature f3-cells.